S-omeprazole magnesium, the generic name for magnesium bis(5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole), is a well-known gastric proton-pump inhibitor and has been commercially available from AstraZeneca under the brand name NEXIUM since 2001.
The S-enantiomer of omeprazole was prepared by separation of diastereoisomeric mixtures of derivatized omeprazole with further conversion to S-omeprazole isolated as an syrupous substance in WO 92/08716.
A more convenient procedure for preparation of single isomer was done by chiral oxidation of a starting sulphide by cumene peroxide in the presence of titanium catalyst, diethyl tartrate and a base. The process is disclosed in WO 96/02535. The enantioselectivity of the foregoing transformation was high but there was still a need for removing residual (R)-enantiomer and overoxidation products like sulfones.
WO 97/02261 describes a method of further enrichment of S-enantiomer of omeprazole from already partially enriched mixtures by precipitating the racemate in selected solvents.
WO 97/02261 describes enzymatic enantioresolution of omeprazole and an analytical HPLC procedure of enantiomer determination.
WO 03/089408 describes a procedure of removing overoxidation products by extraction of S-enantiomer of omeprazole with water solution having selected pH values.
WO 94/27988 describes a solid form of S-omeprazole magnesium.
WO 95/01977 describes solid omeprazole magnesium with a degree of crystallinity over 70%.
WO 97/41114 describes an improved procedure for preparing omeprazole magnesium and S-omeprazole magnesium with a low content of inorganic impurities.
WO 04/046134 describes an amorphous S-omeprazole magnesium salt in the form of a trihydrate wherein the term trihydrate is used to define a crystalline material in which water molecules are bound in the crystalline lattice.
WO 03/051867 describes separating omeprazole enantiomers by using simulated moving bed chromatography. Separation requires using technologically demanding procedures of chiral column chromatography to provide enantioresolution of 2-pyridinylmethylsulfinyl-1H-benzimidazoles.
Despite the foregoing, there continues to be a need for a process that can be used to prepare S-omeprazole magnesium with high chemical and optical purity on an industrial scale in a technological simple and efficient way.